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The Polyfunctionality of Human Memory CD8+ T Cells Elicited by Acute and Chronic Virus Infections Is Not Influenced by Age

As humans age, they experience a progressive loss of thymic function and a corresponding shift in the makeup of the circulating CD8+ T cell population from naïve to memory phenotype. These alterations are believed to result in impaired CD8+ T cell responses in older individuals; however, evidence th...

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Autores principales: Lelic, Alina, Verschoor, Chris P., Ventresca, Mario, Parsons, Robin, Evelegh, Carole, Bowdish, Dawn, Betts, Michael R., Loeb, Mark B., Bramson, Jonathan L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521721/
https://www.ncbi.nlm.nih.gov/pubmed/23271970
http://dx.doi.org/10.1371/journal.ppat.1003076
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author Lelic, Alina
Verschoor, Chris P.
Ventresca, Mario
Parsons, Robin
Evelegh, Carole
Bowdish, Dawn
Betts, Michael R.
Loeb, Mark B.
Bramson, Jonathan L.
author_facet Lelic, Alina
Verschoor, Chris P.
Ventresca, Mario
Parsons, Robin
Evelegh, Carole
Bowdish, Dawn
Betts, Michael R.
Loeb, Mark B.
Bramson, Jonathan L.
author_sort Lelic, Alina
collection PubMed
description As humans age, they experience a progressive loss of thymic function and a corresponding shift in the makeup of the circulating CD8+ T cell population from naïve to memory phenotype. These alterations are believed to result in impaired CD8+ T cell responses in older individuals; however, evidence that these global changes impact virus-specific CD8+ T cell immunity in the elderly is lacking. To gain further insight into the functionality of virus-specific CD8+ T cells in older individuals, we interrogated a cohort of individuals who were acutely infected with West Nile virus (WNV) and chronically infected with Epstein Barr virus (EBV) and Cytomegalovirus (CMV). The cohort was stratified into young (<40 yrs), middle-aged (41–59 yrs) and aged (>60 yrs) groups. In the aged cohort, the CD8+ T cell compartment displayed a marked reduction in the frequency of naïve CD8+ T cells and increased frequencies of CD8+ T cells that expressed CD57 and lacked CD28, as previously described. However, we did not observe an influence of age on either the frequency of virus-specific CD8+ T cells within the circulating pool nor their functionality (based on the production of IFNγ, TNFα, IL2, Granzyme B, Perforin and mobilization of CD107a). We did note that CD8+ T cells specific for WNV, CMV or EBV displayed distinct functional profiles, but these differences were unrelated to age. Collectively, these data fail to support the hypothesis that immunosenescence leads to defective CD8+ T cell immunity and suggest that it should be possible to develop CD8+ T cell vaccines to protect aged individuals from infections with novel emerging viruses.
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spelling pubmed-35217212012-12-27 The Polyfunctionality of Human Memory CD8+ T Cells Elicited by Acute and Chronic Virus Infections Is Not Influenced by Age Lelic, Alina Verschoor, Chris P. Ventresca, Mario Parsons, Robin Evelegh, Carole Bowdish, Dawn Betts, Michael R. Loeb, Mark B. Bramson, Jonathan L. PLoS Pathog Research Article As humans age, they experience a progressive loss of thymic function and a corresponding shift in the makeup of the circulating CD8+ T cell population from naïve to memory phenotype. These alterations are believed to result in impaired CD8+ T cell responses in older individuals; however, evidence that these global changes impact virus-specific CD8+ T cell immunity in the elderly is lacking. To gain further insight into the functionality of virus-specific CD8+ T cells in older individuals, we interrogated a cohort of individuals who were acutely infected with West Nile virus (WNV) and chronically infected with Epstein Barr virus (EBV) and Cytomegalovirus (CMV). The cohort was stratified into young (<40 yrs), middle-aged (41–59 yrs) and aged (>60 yrs) groups. In the aged cohort, the CD8+ T cell compartment displayed a marked reduction in the frequency of naïve CD8+ T cells and increased frequencies of CD8+ T cells that expressed CD57 and lacked CD28, as previously described. However, we did not observe an influence of age on either the frequency of virus-specific CD8+ T cells within the circulating pool nor their functionality (based on the production of IFNγ, TNFα, IL2, Granzyme B, Perforin and mobilization of CD107a). We did note that CD8+ T cells specific for WNV, CMV or EBV displayed distinct functional profiles, but these differences were unrelated to age. Collectively, these data fail to support the hypothesis that immunosenescence leads to defective CD8+ T cell immunity and suggest that it should be possible to develop CD8+ T cell vaccines to protect aged individuals from infections with novel emerging viruses. Public Library of Science 2012-12-13 /pmc/articles/PMC3521721/ /pubmed/23271970 http://dx.doi.org/10.1371/journal.ppat.1003076 Text en © 2012 Lelic et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lelic, Alina
Verschoor, Chris P.
Ventresca, Mario
Parsons, Robin
Evelegh, Carole
Bowdish, Dawn
Betts, Michael R.
Loeb, Mark B.
Bramson, Jonathan L.
The Polyfunctionality of Human Memory CD8+ T Cells Elicited by Acute and Chronic Virus Infections Is Not Influenced by Age
title The Polyfunctionality of Human Memory CD8+ T Cells Elicited by Acute and Chronic Virus Infections Is Not Influenced by Age
title_full The Polyfunctionality of Human Memory CD8+ T Cells Elicited by Acute and Chronic Virus Infections Is Not Influenced by Age
title_fullStr The Polyfunctionality of Human Memory CD8+ T Cells Elicited by Acute and Chronic Virus Infections Is Not Influenced by Age
title_full_unstemmed The Polyfunctionality of Human Memory CD8+ T Cells Elicited by Acute and Chronic Virus Infections Is Not Influenced by Age
title_short The Polyfunctionality of Human Memory CD8+ T Cells Elicited by Acute and Chronic Virus Infections Is Not Influenced by Age
title_sort polyfunctionality of human memory cd8+ t cells elicited by acute and chronic virus infections is not influenced by age
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521721/
https://www.ncbi.nlm.nih.gov/pubmed/23271970
http://dx.doi.org/10.1371/journal.ppat.1003076
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